[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 34.204.191.0. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Views 2,573
Citations 0
Original Investigation
February 6, 2020

Association of Maximal Extent of Resection of Contrast-Enhanced and Non–Contrast-Enhanced Tumor With Survival Within Molecular Subgroups of Patients With Newly Diagnosed Glioblastoma

Author Affiliations
  • 1Department of Neurological Surgery, University of California, San Francisco
  • 2Department of Neurological Surgery, Oregon Health Sciences University, Portland
  • 3Department of Pathology, University of California, San Francisco
  • 4Department of Radiology and Biomedical Imaging, University of California, San Francisco
  • 5Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia
  • 6Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio
  • 7Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas
  • 8Department of Radiology, University Hospitals of Cleveland, Cleveland, Ohio
  • 9Research Division, University Hospitals of Cleveland, Cleveland, Ohio
  • 10Seidman Cancer Center, University Hospitals of Cleveland, Cleveland, Ohio
  • 11Mayo Clinic, Rochester, Minnesota
  • 12Department of Neurology, University of California, San Francisco
JAMA Oncol. Published online February 6, 2020. doi:10.1001/jamaoncol.2019.6143
Key Points

Question  Is maximal extent of resection of non–contrast-enhanced and contrast-enhanced tumor associated with improved survival within molecularly defined subgroups of newly diagnosed glioblastoma?

Findings  In this cohort study of 761 patients with newly diagnosed glioblastoma, maximal resection of contrast-enhanced plus non–contrast-enhanced tumor was found to be associated with increased overall survival in younger patients, whereas maximal resection of contrast-enhanced tumor was associated with increased overall survival in older patients, regardless of molecular subgroup.

Meaning  These findings indicate that maximal extent of resection of the contrast-enhanced tumor in all patients and the contrast-enhanced plus non–contrast-enhanced tumor in younger patients is associated with increased overall survival regardless of molecular subgroup and suggest a need to reconsider surgical strategies for these patients in the molecular era.

Abstract

Importance  Per the World Health Organization 2016 integrative classification, newly diagnosed glioblastomas are separated into isocitrate dehydrogenase gene 1 or 2 (IDH)–wild-type and IDH-mutant subtypes, with median patient survival of 1.2 and 3.6 years, respectively. Although maximal resection of contrast-enhanced (CE) tumor is associated with longer survival, the prognostic importance of maximal resection within molecular subgroups and the potential importance of resection of non–contrast-enhanced (NCE) disease is poorly understood.

Objective  To assess the association of resection of CE and NCE tumors in conjunction with molecular and clinical information to develop a new road map for cytoreductive surgery.

Design, Setting, and Participants  This retrospective, multicenter cohort study included a development cohort from the University of California, San Francisco (761 patients diagnosed from January 1, 1997, through December 31, 2017, with 9.6 years of follow-up) and validation cohorts from the Mayo Clinic (107 patients diagnosed from January 1, 2004, through December 31, 2014, with 5.7 years of follow-up) and the Cleveland Clinic’s Ohio Brain Tumor Study (99 patients with data collected from January 1, 2008, through December 31, 2011, with a median follow-up of 10.9 months). Image accessors were blinded to patient groupings. Eligible patients underwent surgical resection for newly diagnosed glioblastoma and had available survival, molecular, and clinical data and preoperative and postoperative magnetic resonance images. Data were analyzed from November 15, 2018, to March 15, 2019.

Main Outcomes and Measures  Overall survival.

Results  Among the 761 patients included in the development cohort (468 [61.5%] men; median age, 60 [interquartile range, 51.6-67.7] years), younger patients with IDH–wild-type tumors and aggressive resection of CE and NCE tumors had survival similar to that of patients with IDH-mutant tumors (median overall survival [OS], 37.3 [95% CI, 31.6-70.7] months). Younger patients with IDH–wild-type tumors and reduction of CE tumor but residual NCE tumors fared worse (median OS, 16.5 [95% CI, 14.7-18.3] months). Older patients with IDH–wild-type tumors benefited from reduction of CE tumor (median OS, 12.4 [95% CI, 11.4-14.0] months). The results were validated in the 2 external cohorts. The association between aggressive CE and NCE in patients with IDH–wild-type tumors was not attenuated by the methylation status of the promoter region of the DNA repair enzyme O6-methylguanine-DNA methyltransferase.

Conclusions and Relevance  This study confirms an association between maximal resection of CE tumor and OS in patients with glioblastoma across all subgroups. In addition, maximal resection of NCE tumor was associated with longer OS in younger patients, regardless of IDH status, and among patients with IDH–wild-type glioblastoma regardless of the methylation status of the promoter region of the DNA repair enzyme O6-methylguanine-DNA methyltransferase. These conclusions may help reassess surgical strategies for individual patients with newly diagnosed glioblastoma.

Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    ×